When Raquel attended a dermatology follow-up appointment, her physician explained that her care would now also involve an endocrinologist and a surgeon. Emerging evidence suggests that factors such as diabetes, metabolic dysfunction, and genetic predisposition may play important roles in the development and progression of hidradenitis suppurativa (HS). The shift in her care reflects this evolving understanding. Increasingly, the focus is moving beyond the skin as new approaches emerge to address this systemic multifactorial inflammatory disease.

This new approach highlights the complex interactions among the immune system, metabolic factors, and genetic predisposition that underlie HS.

HS, also known as acne inversa, is a chronic inflammatory skin disease that causes painful nodules, recurring abscesses, and sinus tracts (tunnels) deep beneath the skin. It primarily affects areas where the skin rubs together and where apocrine glands are located, such as the axillae, groin, and anogenital regions. HS can be highly debilitating and has a substantial impact on quality of life.

Although it was once thought to result from infection of the apocrine glands, current evidence indicates that the disease begins with abnormal keratinization that blocks the follicle, leading to follicular rupture and a persistent dysregulated immune response.

This process activates inflammatory pathways involving TNF-alpha, interleukin (IL)-1-beta, and IL-17, promoting chronic inflammation and tissue damage.

HS affects approximately 1% of the population, occurs more commonly in women, and typically develops after puberty. However, the true prevalence may be higher because the condition remains substantially underdiagnosed.

Genetic Contribution

Although genetics was once considered a secondary factor, a 2024 review found that approximately 30% of patients reported a family history of HS.

Evidence supporting monogenic inheritance remains limited, accounting for < 7% of cases.

Among the genes implicated in HS, NCSTN and PSENEN are associated with the gamma-secretase complex, a key pathway involved in hair follicle regulation and cellular signaling. Mutations in these genes have been linked to earlier onset of the disease and, generally, more severe forms of the disease.

The current consensus suggests that these cases are only a minority of patients. Most individuals with HS do not have a single identifiable causative mutation, supporting the hypothesis that HS is predominantly a polygenic disease in which multiple genetic variants interact with one another and environmental factors.

Environmental Factors

Environmental influences also appear to play a major role in the development and progression of HS.

Accumulating evidence primarily points to smoking and other metabolic disorders.

A meta-analysis published in the International Wound Journal in 2024 reported associations between HS and smoking, obesity, and diabetes.

More recently, a 2026 study published in JAMA Dermatology using a genetic causal framework suggested that BMI may have a direct effect on HS risk and reinforced the substantial contribution of smoking.

Although the researchers cautioned that these findings do not establish absolute causality in every case, they concluded that weight management and smoking cessation should be considered essential components of HS treatment.

A growing body of evidence has influenced recent clinical guidance. The 2024-2025 European S2K guidelines noted that advances in understanding HS pathophysiology have been substantial enough to redefine both diagnostic and treatment algorithms.

Within this updated framework, chronic inflammation is viewed as the central disease mechanism, while infection is regarded primarily as a secondary complication rather than the primary therapeutic target.

Biologics and Surgery

This shift in understanding has transformed treatment strategies. Where antibiotics once dominated management, biological therapies targeting specific immune pathways now play a significant role in moderate-to-severe HS.

Three biological therapies are currently approved in Europe for HS treatment: adalimumab, secukinumab, and bimekizumab.

Recent results from BE HEARD I and II clinical trials and their extension studies showed that bimekizumab produced sustained improvements in inflammatory lesions, pain, and quality of life for up to 2 years.

Secukinumab has also shown durable responses in some patients for as long as 4 years, supporting its growing role in clinical practice.

Surgery remains an important treatment choice, particularly for patients with advanced diseases and extensive sinus tract involvement.

However, surgery is no longer viewed solely as a rescue intervention. Current European guidelines support combining surgical approaches with biological therapy according to disease phenotype and severity, using a personalized, stepwise treatment strategy.

Spanish Registry

To better understand HS in routine clinical practice, the Spanish Academy of Dermatology and Venereology launched the Spanish Registry of Hidradenitis Suppurativa (REHS).

This registry aims to evaluate treatment effectiveness and safety in real-world settings, identify prognostic factors, and assess the impact of earlier diagnosis.

During its first year, the REHS enrolled 359 patients from 23 centers.

The average patient age was 37 years, and 53% of the patients were women. More than 70% were current or former smokers, approximately one third reported a family history of HS, and nearly 20% had already received biologic therapy.

These data reflect the clinical profile of the disease and highlight the importance of potentially modifiable risk factors.

Raquel is now part of this registry and has transitioned from skin-focused treatment to multidisciplinary care for a condition that is far more complex than it first appeared. What was once viewed primarily as a skin disease is now recognized as a systemic inflammatory disorder that often requires coordinated care across multiple specialties. Despite advances in understanding and treatment, many patients still face years of diagnostic delays.

This article was translated from El Médico Interactivo on Univadis, part of the Medscape Professional Network.